The attachment of organic molecules to silicon surfaces is of particular usefulness in a number of technologies and products that involve silicon-based components. For example, organic molecule monolayers may serve as active components in hybrid molecule/silicon electronic devices, as lubrication and anti-stiction coatings in silicon based microelectromechanical systems (MEMS), as masking layer in soft lithography, and as molecular linkages in Si-based chips for gene analysis.
Various methods of Si surface attachment chemistry have been reported, including (i) hydrosilation between alkenes and hydrogen-terminated Si (Linford and Chidsey, U.S. Pat. No. 5,429,708; Linford and Chidsey, J. Am. Chem. Soc. 1993, 115; Linford et al., J. Am. Chem. Soc. 1995, 117); (ii) the reaction of metal organic reagents with H- or Cl-terminated silicon surfaces (Bansal et al., J. Am. Chem. Soc. 1996, 118; He et al. Chem. Phys. Lett. 1998, 286; Kim and Laibinis, J. Am. Chem. Soc. 1999, 121); (iii) cyclo-addition reactions on clean Si(100) in which the Sixe2x95x90Si surface dimer reacts with Cxe2x95x90C or Cxe2x95x90Cxe2x80x94Cxe2x95x90C to form 4- and 6-membered rings, respectively (Hamers et al., U.S. Pat. No. 5,908,692; Hamers et al., J. Phys. Chem. B 1997, 101; Teplyakov et al., J. Am. Chem. Soc. 1997, 119): and (iv) the electrochemical grafting of hydrocarbon radicals with H-terminated silicon (de Villeneuve et al. J. Phys. Chem. B 1997, 101). There have been attempts at grafting organic molecules from the dissociative adsorption of amines on clean Si (Kugler et al., Surf. Sci. 1992, 260) and alcohols on H-terminated Si (Cleland, et al., J. Chem. Soc. Faraday Tran. 1995, 91; Glass, et al. Sur Sci. 1995, 338). In addition, there have been reports on photoinitiated reactions of organic molecules with H-terminated silicon surfaces (Effenberger, et al. Angew. Chem. Int. Ed. 1998, 37; Lee et al. J. Am. Chem. Soc. 1996, 118).
These assembly processes have various shortcomings. For example, the cyclo-addition reaction can yield well-ordered organic layers but requires clean Si(100) in ultra-high vacuum (UHV) environment. The use of organolithium or Grignard reagent may not be compatible with some semiconductor processes where metal contamination of the surface must be avoided. The high reactivity of these reagents also limits the possibility of functional groups in organic molecules. The hydrosilation process yields dense organic layers but works only in the solution phase and reaction rates are relatively slow. The electrochemical method is limited to a small number of radical species that can be generated in the solution phase. All the above methods are based on the covalent Sixe2x80x94C linkage, which restricts the possibilities of surface chemistry. Other methods based on dissociative adsorption resulted in incomplete organic layers and those using photoactivation were limited to illuminated areas.
Moreover, silicon surface chemistry is of particular interest within the field of biomedical research, wherein the use of Si-based chips for analytical procedures has great benefit in the ability to carry out and/or monitor arrays of assays. Examples include: high-throughput screening for new pharmaceuticals and other chemical entities, toxicology screening, and gene expression screening and analysis, clinical assays, microbiological analysis, environmental testing, food and agricultural analysis, genetic screening, monitoring chemical and biological warfare agents, and process control. Each of these applications involves carrying out and monitoring a reaction where a binding reagent is contacted with a test sample, and the occurrence and extent of binding of the binding reagent with specific components (target moieties) within the test sample is measured in some form. Such chips are described in U.S. Pat. No. 5,843,767 the specification of which are incorporated herein by reference in its entirety.
One widely used analytical procedure in genome mapping illustrative of such applications is hybridization of membrane-immobilized DNAs with labeled DNA probes. Robotic devices currently enable gridding of 10,000-15,000 different target DNAs onto a 12 cmxc3x978 cm membrane. See for example, Drmanac et al. in Adams et al. (Eds.), Automated DNA Sequencing and Analysis, Academic Press, London, 1994 and Meier-Ewert et al. Science 361:375-376 (1993). Hybridization of DNA probes to such membranes has numerous applications in genome mapping, including generation of linearly ordered libraries, mapping of cloned genomic segments to specific chromosomes or mega YACs, cross connection of cloned sequences in cDNA and genomic libraries, and so forth.
Genosensors, or miniaturized xe2x80x9cDNA chipsxe2x80x9d currently are being developed for detection of multiple binding reactions such as hybridization analysis of DNA samples. DNA chips typically employ arrays of DNA probes tethered to flat surfaces to acquire a hybridization pattern reflecting the nucleotide sequence of the target DNA. See, for example, Fodor et al. Science, 251:767-773 (1991); Southern et al. Genomics 13:1008-1017 (1992); Eggers et al. Advances in DNA Sequencing Technology, SPIE Conference, Los Angeles, Calif. (1993); and Beattie et al. Clin. Chem. 39:719-722 (1993). Such devices may be applied in carrying out and monitoring other binding reactions, such as antibody capture and receptor binding reactions.
However, miniaturization of DNA hybridization arrays or other types of binding arrays on silicon surfaces or other two-dimensional surfaces comprising silicon has been limited by the paucity of methodologies for attaching organic targeting molecules to the silicon surface.
It is apparent, therefore that more convenient and general methods for attaching organic molecules to silicon surfaces are desirable. Methods that are more efficient, and impart fewer limitations on surface chemistry are particularly desirable.
It is therefore an object of the present invention to provide methods that greatly increase the efficiency for the attachment of organic molecules on silicon.
In accomplishing the foregoing object of the invention, there has been provided, in accordance with one aspect of the invention, a method for attaching organic molecules to a silicon surface comprising reacting an organic molecule containing nucleophilic functionality with a halogenated silicon surface.
In an embodiment of the invention, the method of the present invention can be performed in solution phase or in a substantially vacuum environment via a gas-surface reaction.
In another embodiment of the invention, there is provided a method for preparing a halogenated silicon surface by reacting a silicon surface with a halogen source to form a halogenated silicon surface.
There is also provided, in yet another aspect of the invention, a surface material comprising an organic molecule covalently bonded to a silicon surface, wherein said surface material is produced by a process comprising reacting a nucleophilic organic molecule with a halogenated silicon surface.
In yet another aspect of the invention there is provided a method of producing an improved device for detecting multiple binding reactions comprising reacting an organic molecule containing a nucleophilic functionality with a halogenated silicon surface of said device. In a preferred embodiment, the organic molecule is a binding reagent effective for sequence analysis by hybridization, analysis of patterns of gene expression by hybridization of mRNA or cDNA to gene-specific probes, immunochemical analysis of protein mixtures, epitope mapping, assay of receptor-ligand interactions and profiling of cellular populations involving binding of cell surface molecules to specific ligands or receptors. In another embodiment, the organic molecule is capable of linking to a binding reagent
In further embodiments, the binding reagents are selected from the group consisting of DNA, proteins and ligands, and in a particular embodiment are oligonucleotide probes.
In yet another preferred embodiment, the binding reagents are attached within densely packed channels of a solid substrate.
Other objects, features and advantages of the present invention will become apparent from the following detailed description. It should be understood, however, that the detailed description and the specific examples, while indicating preferred embodiments of the invention, are given by way of illustration only, since various changes and modifications within the spirit and scope of the invention will become apparent to those skilled in the art from this detailed description.